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Abstract

Objective

To compare pharmacokinetics of eltenac after first and last IV administrations (0.5 mg/kg), using a multiple dosing schedule.

Animals

6 adult mares.

Procedure

Eltenac (50 mg/ml) was administered IV at a dosage of 0.5 mg/kg of body weight every 24 hours for days 0 through 4. On days 0 and 4, blood samples were collected before, then periodically for 8 hours after eltanac administration. Concentration of eltenac in plasma samples was determined by use of high-performance liquid chromatography.

Results

On day 0, median area under the plasma eltenac concentration versus time curve (AUC) was 6.77 μg•h/ml (range, 5.61 to 8.08 μg•h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.03 to 1.40 ml/min/kg), and median steady-state volume of distribution was 191 ml/kg (range, 178 to 218 ml/kg). Median terminal half-life of eltenac was 2.36 hours (range, 2.30 to 2.98 hours). On day 4, median eltenac AUC was 6.70 μg•h/ml (range, 5.21 to 7.44 μg•h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.12 to 1.53 ml/min/kg), and median steady-state volume of distribution was 193 ml/kg (range, 172 to 205 ml/kg). Median terminal half-life of eltenac was 2.40 hours (range, 2.11 to 3.25 hours). Protein binding of eltenac, determined by ultrafiltration, was > 99% at a total plasma concentration of 36 μg/ml.

Conclusion

Pharmacokinetic variables determined for each horse were not different between days 0 and 4.

Clinical Relevance

Under conditions of this study, there was no clinically relevant accumulation of eltenac in equine plasma or alteration of pharmacokinetic variables after multiple IV dosing of 0.5 mg/kg of eltenac. (Am J Vet Res 1998;59:1447–1450)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To measure renal clearance of antipyrine and urinary excretion of antipyrine (AP) metabolites in horses by use of validated high-performance liquid chromatography (HPLC) methods.

Animals

8 Standardbred mares.

Procedure

HPLC methods for measurement of AP in equine plasma and AP and its metabolites in equine urine were validated. Antipyrine (20 mg/kg of body weight) was administered IV, and blood samples and urine specimens were collected over 24 hours.

Results

Median plasma clearance of AP in horses was 6.2 ml/min/kg, of which < 2% could be attributed to renal clearance. Urinary excretion of AP and its metabolites over 24 hours accounted for < 22% of the AP dose administered. The major metabolite of AP in urine was 4-hydroxyantipyrine.

Conclusions and Clinical Relevance

Use of the proven validated methods for measuring AP and its metabolites indicated that AP has minimal renal clearance in horses, suggesting that plasma clearance of AP reflects hepatic clearance. Combined with AP metabolite data, the pharmacokinetics of AP may be useful for assessment of hepatic cytochrome P450 activity in horses. (Am J Vet Res 1998;59:280–285)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine the effects of acute exercise on hepatic blood flow by studying hepatic clearance of bromsulphalein for several submaximal exercise intensities.

Animals

8 adult Standardbred mares.

Procedure

Horses were subjected to 4 submaximal exercise intensities (resting and 40, 60, and 80% maximal oxygen consumption). After horses had been running at the required treadmill speed for 1 minute, bromsulphalein (BSP; 5 mg/kg of body weight, IV) was administered during a 45- to 60-second period, and horses continued at the desired speed for an additional 15 minutes. Blood samples were collected at 2-minute intervals for 30 minutes, and plasma concentration of BSP was determined by spectrophotometry. Estimates of pharmacokinetic variables were compared among the 4 exercise intensities, using a Friedman repeated-measures analysis on ranks and linear regression.

Results

Median values for clearance of BSP from blood and plasma decreased significantly with exercise and was linearly related to exercise intensity. Exercise-induced differences were not detected in the volume of distribution of BSP. Elimination half-life of BSP increased significantly with increasing exercise intensity and was linearly related to exercise intensity.

Conclusions

Acute submaximal exercise has a dramatic effect on clearance of BSP in horses. Presumably, exercise-induced decreases in splanchnic blood flow limit blood flow to the liver, decreasing hepatic clearance of BSP and leading to persistence of plasma concentrations of BSP.

Clinical Implications

Drugs that are efficiently extracted by the liver may have decreased hepatic clearance when horses exercise at submaximal intensities. (Am J Vet Res 1998;59:1481–1487)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine the radiographic methods that best predict the development of osteoarthritis in the hip joints of a cohort of dogs with hip dysplasia and unaffected dogs.

Animals—205 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbred dogs.

Procedure—Pelvic radiography was performed when the dogs were 8 months old. Ventrodorsal extendedhip, distraction, and dorsolateral subluxation (DLS) radiographs were obtained. An Orthopedic Foundation for Animals-like hip score, distraction index, dorsolateral subluxation score, and Norberg angle were derived from examination of radiographs. Osteoarthritis was diagnosed at the time of necropsy in dogs ≥ 8 months of age on the basis of detection of articular cartilage lesions. Multiple logistic regression was used to determine the radiographic technique or techniques that best predicted development of osteoarthritis.

Results—A combination of 2 radiographic methods was better than any single method in predicting a cartilage lesion or a normal joint, but adding a third radiographic method did not improve that prediction. A combination of the DLS score and Norberg angle best predicted osteoarthritis of the hip joint or an unaffected hip joint. All models that excluded the DLS score were inferior to those that included it.

Conclusions and Clinical Relevance—A combination of the DLS score and Norberg angle was the best predictor of radiographic measures in 8-month-old dogs to determine whether a dog would have normal or osteoarthritic hip joints. (Am J Vet Res 2003;64:1472–1478)

Full access
in American Journal of Veterinary Research